scholarly journals Evaluation of Tissue and Circulating miR-21 as Potential Biomarker of Response to Chemoradiotherapy in Rectal Cancer

2020 ◽  
Vol 13 (9) ◽  
pp. 246
Author(s):  
Susana Ourô ◽  
Cláudia Mourato ◽  
Marisa P. Ferreira ◽  
Diogo Albergaria ◽  
André Cardador ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Tissue ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Recurrence Risk ◽  
Locally Advanced Rectal Cancer ◽  
Plasma Biomarker ◽  
Potential Biomarker

Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre- and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40–6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45–7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.

Acid Ceramidase As A Potential Biomarker For Locally Advanced Rectal Cancer; Is Apoptosis The Mechanism?

2019 ◽  
Vol 45 (11) ◽  
pp. 2214
Author(s):  
Rachael Clifford ◽  
Naren Govindarajah ◽  
David Bowden ◽  
Paul Sutton ◽  
Jason Parsons ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Acid Ceramidase ◽  
Potential Biomarker

scholarly journals The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7040 ◽  
Author(s):  
Fatima Domenica Elisa De Palma ◽  
Gaetano Luglio ◽  
Francesca Paola Tropeano ◽  
Gianluca Pagano ◽  
Maria D’Armiento ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Decision Making ◽  
Locally Advanced ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Clinical Decision ◽  
Locally Advanced Rectal Cancer ◽  
Specific Expression ◽  
Micro Rnas

The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

Pilot Study of Patients’ Preferences for Immediate Resection Versus a Watch and Wait Approach After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

2020 ◽  
pp. OP.20.00158
Author(s):  
Ashray Gunjur ◽  
Grace Chazan ◽  
Genni Newnham ◽  
Sue-Anne McLachlan
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Recurrence Risk ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Watch And Wait ◽  
Time Tradeoff

PURPOSE: In patients with rectal cancer who achieve a clinical complete response to neoadjuvant chemoradiation, it may be reasonable to adopt a watch-and-wait (W&W) strategy rather than proceed to immediate resection of the rectum. Patient preferences for this strategy are unknown. The primary aim of the current study was to determine the feasibility of assessing hypothetical recurrence and survival differences that relevant patients would tolerate to avoid immediate resection of the rectum. A secondary aim included estimating patients’ tolerance thresholds and the factors that might predict them. METHODS: We developed a study-specific written questionnaire based on a previously validated instrument. Hypothetical time tradeoff tasks were used to determine the recurrence rate patients would accept to adopt a W&W strategy and the survival benefit that would be needed to justify choosing immediate resection over W&W. Feasibility was measured on the basis of response rate, the stated ease of completion and the satisfaction of task, and time used. RESULTS: Twenty of 31 potentially eligible patients completed the study-specific questionnaire. The majority of respondents felt that questions were clear (70%) and not hard to understand (65%). The median acceptable recurrence risk to adopt a W&W strategy was 20% (interquartile range [IQR], 10%-35%). Patients required a median of 2.0 extra years of survival (IQR, 1.0-3.0 years) over a baseline 7.0 years, and they required a median extra 10% (IQR, 4%-19%) over baseline 70% survival rates to justify immediate resection. CONCLUSION: Measuring the preferences of patients with rectal cancer using time tradeoff methods seemed to be feasible. Larger studies are needed to confirm how acceptable a W&W strategy would be for relevant patients.

scholarly journals Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Raquel Conde-Muíño ◽  
Marta Cuadros ◽  
Natalia Zambudio ◽  
Inmaculada Segura-Jiménez ◽  
Carlos Cano ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Surgical Techniques ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
High Local Recurrence Rate

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile’s ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

scholarly journals Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4642
Author(s):  
Tomoyuki Momma ◽  
Hirokazu Okayama ◽  
Yasuyuki Kanke ◽  
Satoshi Fukai ◽  
Hisashi Onozawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Gene Signature ◽  
Locally Advanced Rectal Cancer ◽  
Predictive Values

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response.

Topoisomerase I expression in locally advanced rectal cancer as predictive marker for response to preoperative chemoradiation

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14566-14566
Author(s):  
K. E. Horisberger ◽  
R. D. Hofheinz ◽  
B. Muessle ◽  
P. Findeisen ◽  
A. Hochhaus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Topoisomerase I ◽  
Tumor Tissue ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Pcr Analysis ◽  
Good Responder

14566 Background: In locally advanced rectal cancer combined modality treatment has become the standard therapeutical intervention. Preoperative downstaging is known as a predictor concerning lower local recurrence rate and probably better overall-survival. However, efficacy of neoadjuvant chemoradiation is compromised in some patients by so far unknown factors. The aim of the present study was to investigate topoisomerase I expression as a potential parameter for predicting response to irinotecan-based chemoradiation. Methods: 15 patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive weekly neoadjuvant irinotecan (1 hour before radiation) and capecitabine as well as cetuximab with a concurrent RT dose of 50.4 Gy (45+5.4 Gy). Surgery was scheduled 4–6 weeks after the completion of chemoradiation. Samples of normal and tumor tissues of all patients were collected before neoadjuvant treatment. Initially, RNA-oligonucleotid-array of three patients (one good responder and two non-responders) was accomplished to show qualitatively different gene expression. To quantify the differences, real-time PCR of topoisomerase I was performed. Results: The differences of gene expression in the RNA-oligonucletoidarray were correlated to the clinical response to neoadjuvant chemoradiation as topoisomerase I showed a significant higher expression in the tumor tissue of the good responder before treatment (p<0.0001). PCR-analysis showed a relatively higher median expression of topoisomerase I in normal tissue (1.7 vs. 0.9; p=0.85) and in tumor tissue (1.5 vs. 1.3; p=0.36) of the subsequent good responding patients (n=10). Conclusion: Patients respond differentially to chemoradiation in terms of clinical response and gene expression shifts. The oligonucleotidarray results leads us to assume that response may be predictable. The preliminary results of PCR demonstrate that TopoI expression describes a valuable parameter for prediction of efficiency of irinotecan in advanced rectal cancer. The small number of patients may have caused the missing of the statistical significance. We are intending an extension of the PCR analysis to more powerful series based on the achievements of the current investigation results. No significant financial relationships to disclose.

Acid ceramidase: a potential biomarker for locally advanced rectal cancer

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
Rachael Elizabeth Clifford ◽  
Naren Govindarajah ◽  
David Bowden ◽  
Paul Sutton ◽  
Jason Parsons ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Acid Ceramidase ◽  
Potential Biomarker

scholarly journals MRI Radiomics Signature as a Potential Biomarker for Predicting KRAS Status in Locally Advanced Rectal Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
ZhiYuan Zhang ◽  
LiJun Shen ◽  
Yan Wang ◽  
Jiazhou Wang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Characteristic Curve ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Image Features ◽  
Lasso Regression ◽  
Wild Type ◽  
Potential Biomarker ◽  
T2 Mri

Background and PurposeLocally advanced rectal cancer (LARC) is a heterogeneous disease with little information about KRAS status and image features. The purpose of this study was to analyze the association between T2 magnetic resonance imaging (MRI) radiomics features and KRAS status in LARC patients.Material and MethodsEighty-three patients with KRAS status information and T2 MRI images between 2012.05 and 2019.09 were included. Least absolute shrinkage and selection operator (LASSO) regression was performed to assess the associations between features and gene status. The patients were divided 7:3 into training and validation sets. The C-index and the average area under the receiver operator characteristic curve (AUC) were used for performance evaluation.ResultsThe clinical characteristics of 83 patients in the KRAS mutant and wild-type cohorts were balanced. Forty-two (50.6%) patients had KRAS mutations, and 41 (49.4%) patients had wild-type KRAS. A total of 253 radiomics features were extracted from the T2-MRI images of LARC patients. One radiomic feature named X.LL_scaled_std, a standard deviation value of scaled wavelet-transformed low-pass channel filter, was selected from 253 features (P=0.019). The radiomics-based C-index values were 0.801 (95% CI: 0.772-0.830) and 0.703 (95% CI: 0.620-0.786) in the training and validation sets, respectively.ConclusionRadiomics features could differentiate KRAS status in LARC patients based on T2-MRI images. Further validation in a larger dataset is necessary in the future.

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